Micro-extraction of chlordiazepoxide and its primary metabolites, desmethylchlordiazepoxide and demoxepam, from plasma and their measurement by liquid chromatography.

We have developed a micro-extraction procedure for the analysis of chlordiazepoxide and its two unique metabolites, demoxepam and desmethylchlordiazepoxide, in plasma, using liquid chromatography. The method is both reliable and sensitive for the quantitation of low plasma concentrations of these three compounds. The extraction procedure allows rapid sample processing, which, together with the small sample volume (100 microL), makes it ideal for routine sample handling. The limit of detection for the three compounds ranged from 0.075 to 0.125 mg/L and recovery of the three different benzodiazepines ranged from 87 to 94%. Within- and between-assay coefficients of variation ranged from 3.1-4.5% and from 4.7 to 7.6%, respectively.

Benzodiazepine misuse by drug addicts.

Using a high-performance liquid chromatography method, we measured seven commonly prescribed benzodiazepines (chlordiazepoxide, nitrazepam, nordiazepam, oxazepam, lorazepam, temazepam and diazepam) in 100 urine samples obtained from patients attending the Leeds Addiction Unit. All of the urines selected for investigation were positive for benzodiazepines using an EMIT (Enzyme Immunoassay) screen. Forty-four of the urines contained a range of benzodiazepines, none of which had been prescribed. Nitrazepam was detected most frequently (61 urine samples), but had not been prescribed to any of the patients in this study. Chlordiazepoxide was detected in 49 urine samples, although it had been prescribed to only five patients. Temazepam was detected in 28 urine samples. Fourteen patients providing 21 urine samples had been prescribed temazepam for treatment. However, temazepam was detected in only 14 of these samples. Multiple benzodiazepine abuse was evident from the high rate of detection of unrelated benzodiazepines.